Choline – An Essential Nutrient

I just finished listening to an interesting podcast featuring Dr. Zeisel, a researcher at the NC Nutrition Research Institute.  The interview discussed the body’s need for choline and the impact of some genetic variants on our ability to produce it in the body.  So I decided to dig into this a little more and look at some of the SNPs covered by 23 and Me or AncestryDNA data related to choline.

A little background information…

Choline is involved in several critical roles in the body including:

  • supporting methylation reactions through donating a methyl group (TMG/betaine)
  • formation of acetylcholine, a neurotransmitter and cell-signaling molecule
  • formation of phosphatidylcholine which makes up cell membranes[ref]
  • muscle function [ref]
  • deficiency in choline contributes to non-alcoholic fatty liver disease[ref]

Recent studies of choline levels show:

  • academic achievement in 15-year olds is significantly associated with plasma choline levels [ref]
  • choline plus B-vitamins may increase neuroplasticity and speed recovery after a stroke [ref]
  • crocodile choline may be a treatment of gastric cancer [ref]
  • choline deficiency is correlated to lower bone mineral density [ref]
  • high serum choline concentrations may increase the risk of colon cancer [ref]
Role of Choline in Methylation Cycle. Wikimedia Commons, Public Domain

Generally, people can make some choline in their liver. But some people have genetic variants that reduce their ability to make choline. They need to ensure adequate intake through food or supplements.

Choline is the precursor to acetylcholine, which is a neurotransmitter.  Acetylcholine controls muscles, heart rhythm, and other function.

The FDA gives a recommended adequate intake for adults as 425-550 mg/day.   [ref]

Your body’s need for choline from the diet will depend in part on how much folate you eat and how well your methylation cycle works.  Choline acts as a methyl donor in the methylation cycle, and with low folate or decreased enzyme efficiency in the folate pathways, your choline requirement may increase.

Genetic Variants Related to Choline

PEMT – phosphatidylethanolamine N-methyltransferase

The PEMT pathway is responsible for the body’s production of phosphatidylcholine which is part of the phospholipid bilayer making up the membranes surrounding our cells.  Note that 23andMe does not cover all of the SNPs in PEMT that are relevant to choline levels.

Check your genetic data for rs7946 (23andMe v4, v5)

  • C/C: normal
  • C/T: somewhat decreased PEMT enzyme activity
  • T/T: decreased PEMT enzyme activity [ref]

CHKA – Choline kinase alpha

The choline kinase alpha enzyme is involved in the pathway of reactions that converts choline into phosphatidylcholine (for cell membranes). Choline kinase specifically is the catalyst in the reaction that converts choline into 0-phosphocholine.   The variant below decreases the turnover of dietary methionine into choline. Carriers of the variant are more likely to need dietary choline since they don’t convert dietary protein (methionine) as well.

Check your genetic data for rs10791957 (23andMe v4, v5; AncestryDNA)

  • A/A: reduced turnover of methionine to phosphatidylcholine
  • A/C: reduced turnover of methionine to phosphatidylcholine
  • C/C: normal

“Specifically, the variant appears to decrease the use of dietary choline for PEMT-PC synthesis relative to CDP-PC synthesis. Variant individuals displayed decreased turnover of choline-derived methionine → PEMT-PC over the study period, indicating decreased activity of PEMT relative to women without the variant, and also tended to exhibit lower relative PEMT-PC/CDP-PC enrichment as compared to non-variants.”[ref]
In another study, those with C/C (normal) were found to be “less likely to have clinical symptoms after consuming a low-choline diet.” [ref]

BHMT – Betaine-homocysteine S-methyltransferase

Check your genetic data for rs3733890: (23andMe v4, v5; AncestryDNA)

  •  A/A: lower conversion of choline to betaine and more conversion of choline to CDP-PC [ref]
  • A/G: lower conversion of choline to betaine and more conversion of choline to CDP-PC
  • G/G: normal

“Together, these results indicate that the variant favors the use of dietary choline for CDP-PC synthesis at the expense of betaine synthesis.” [ref]

FMO3 – Flavin-containing monooxygenase

Check your genetic data for rs2266782:  (23andMe v4, v5):

  • A/A: a greater turnover of betaine to methionine and a greater turnover of choline-derived methionine to PEMT-PC
  • A/G:  a greater turnover of betaine to methionine and a greater turnover of choline-derived methionine to PEMT-PC
  • G/G: normal

“While a previous study from our group suggested that the variant might be associated with increased use of choline as a methyl donor in men (based on increased DMG pool size) [43], results from the present study, indicate that women with the variant actually use choline less as a methyl donor. Variant women tended to have a lower turnover of betaine → methionine over the study period. In addition, variant women exhibited a greater turnover of choline-derived methionine → PEMT-PC over the study period, which is consistent with previous findings from our lab that have identified lower methionine excretion among variant individuals (i.e., greater use of methionine may reduce excretion)” [ref]

MTHFD1 – methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1

This is actually an enzyme in the folate pathway, but it affects your need for adequate choline in the diet.

Check your genetic data for rs2236225 (G1958A): (23andMe v.4 and v.5)

  • A/A: decreased MTHFD1 enzyme stability[ref] more of a reliance on choline as a methyl donor
  • A/G: decreased MTHFD1 enzyme stability[ref] more of a reliance on choline as a methyl donor
  • G/G: normal

Carriers of the A allele are more likely to have choline deficiency on a low choline diet (modified by folate intake) [ref] [ref]  In one study with premenopausal women, those with an A-allele were 15 times more likely to show choline deficiency symptoms on a diet low in choline.


Food and supplements:

Excellent (egg-cellent :-) sources of choline in foods include:  eggs, liver, shitake mushrooms, milk, and various meats.  [ref]  Raw egg yolks are a better source of choline than cooked, but there are drawbacks, especially if you don’t know the source of your eggs.

Choline supplement options include CDP-choline, phosphatidylcholine, alpha-GPC, and choline citrate. is a good source of information on the different types of choline.

More to read:

Dr. Amy Yasko also has a lot of information about the role of choline in the methylation cycle.  Her view is that MTHFR variants can be bypassed using choline if a person doesn’t have BHMT or PEMT variants. Her free book Companion Guide: Feel Good Nutrigenomics is a good place to start, and her full book Feel Good Nutrigenomics as well as videos, etc can be found on her website.

Linus Pauling Institute (University of Oregon) – Choline

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4 Comments on “Choline – An Essential Nutrient

  1. I’m finding that upping acetylcholine is being a great help to me. I’m rotating CDP choline and Huperzine A. Having recently learned I’m positive for Lupus Anticoagulant and thinning my blood with herbals and this combination – some very complex issues are greatly improving.

    Here’s a link to a thread on Health rising where some of us are finding this to be beneficial.


  2. I am trying to figure out which choline to take. I am very deficient. My FMO3 t/t,BCHE t/t, I am allergic to sulfur foods and medications. I am scared because so many genes are coming up with Alzheimer, dementia. My MTRR A66g is t/t. Have increased phosphatidyletha-o-amine values, Triphosphatase is t/t. I cannot figure out where the methylation problem is, sulfur or phosphurous? Then how do you help clear the pathway. I have not found a B vitamin I can take. My C677T is t/- , L432V is t/t. How do you follow Choline pathway. I would greatly appreciate any input! So confused

    • I have Molybdenum in high doses initially (1000mcg+) per day to help immensely with sulfur issues.

  3. A very scientific approach to describing Choline, its benefits and how it works. This article is very informative and useful. Thank you for posting this.

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